CLINICAL CHEMISTRY Jolan F.

Herce
BSMT-3B
LECTURE / 2nd SEMESTER
o albumin
The quantity of T4 and T3 in the circulation can be
CHAPTER 23: The Thyroidsignificantly
Gland affected by the amount of binding protein
THE THYROID available for carrying these hormones. For example, high
The thyroid gland is responsible for the production of two estrogen levels during pregnancy lead to increased thyroxine-
hormones: binding protein production by the liver.
1. thyroid hormone - critical in regulating body
metabolism, neurologic development, and numerous other
body functions CONTROL OF THYROID FUNCTION
2. calcitonin - secreted by parafollicular C cells and is involved  hypothalamic–pituitary–thyroid axis
in calcium homeostasis o essential for correctly interpreting thyroid function
testing
THYROID ANATOMY AND DEVELOPMENT o central in the regulation of thyroid hormone
 The thyroid gland is positioned in the lower anterior neck production
and is shaped like a butterfly.  TRH - synthesized by neurons in the supraoptic and
 It is made up of two lobes that rest on each side of the supraventricular nuclei of the hypothalamus and stored in the
trachea, with a band of thyroid tissue—called the isthmus— median eminence of the hypothalamus.
running anterior to the trachea and bridging the lobes.  When secreted, this hormone stimulates cells in the anterior
 Posterior to the thyroid gland are the parathyroid glands pituitary gland to manufacture and release thyrotropin
that regulate serum calcium levels and the recurrent laryngeal (TSH).
nerves that innervate the vocal cords.
 In parts of the world where severe iodine deficiency exists,
neither the mother nor the fetus can produce thyroid hormone
and both develop hypothyroidism.

THYROID HORMONE SYNTHESIS

 Recommended minimum daily intake of Iodine: 150 ug
 ↓ 50 ug daily – hypothyroidism
 The major component of colloid is thyroglobulin, a
glycoprotein manufactured exclusively by thyroid follicular
cells
 Catalyzed by a membrane-bound enzyme called thyroid
peroxidase (TPO), concentrated iodide is oxidized and
bound with tyrosyl residues on thyroglobulin.
 This results in production of monoiodothyronine (MIT) and
diiodothyronine (DIT).
 This same enzyme also aids in the coupling of two tyrosyl
residues to form triiodothyronine (T3)(one MIT residue +
one DIT residue) or thyroxine (T4)(two DIT residues).

ACTIONS OF THYROID HORMONE

 Released from the thyroid gland, circulates in the
bloodstream.
 T4 is deiodinated into T3 (active form of thyroid hormone)
 T3 combines with its nuclear receptor on hormone-responsive
genes, producing messenger RNA and proteins influencing
metabolism and development.
 Effects include tissue growth, brain maturation, increased
heat production, oxygen consumption, and increased β-
adrenergic receptors.

TESTS FOR THYROID EVALUATION

Blood Tests
Thyroid-Stimulating Hormone
 The most useful test for assessing thyroid function is the
HYPOPHYSIOTROPIC OR HYPOTHALAMIC TSH.
PROTEIN BINDING OF THYROID HORMONE  In subclinical hypothyroidism, the TSH is minimally
 When released into the circulation, only 0.04% of T4 and increased while the free T4 stays within the normal range.
0.4% of T3 are unbound by proteins and available for Likewise, in subclinical hyperthyroidism, the TSH is
hormonal activity. suppressed while the free T4 is normal.
 Three major binding proteins:
o thyroxine-binding globulin (TBG) Serum T4 and T3
o thyroxine-binding prealbumin  Serum total T4 and T3 levels are usually measured by
radioimmunoassay (RIA), chemiluminometric assay, or

TRANSCRIBED BY: JOLAN HERCE

CLINICAL CHEMISTRY Jolan F. Herce
BSMT-3B
LECTURE / 2nd SEMESTER
similar immunometric technique. Because more than 99.9% Fine-Needle Aspiration
of thyroid hormone is protein bound, alterations in thyroid
 Thyroid fine-needle aspiration (FNA) biopsy is often
hormone–binding proteins, unrelated to thyroid disease,
the first step and the most accurate tool in the evaluation of
frequently lead to total T4 and T3 levels outside of the
thyroid nodules.
normal range.
 FNA biopsy results are reported according to six categories:
 This assay have been developed to measure free T4 and T3,
nondiagnostic, malignant, suspicious for malignancy,
the biologically active forms of thyroid hormone, and free T4
indeterminate or suspicious for neoplasm, follicular lesion of
kits have replaced total T4 determinations at the clinical
undetermined significance, and benign. These categories
level, secondary to ease of interpretation and lower
dictate subsequent treatment, ranging from routine ultrasound
processing cost.
monitoring to surgical excision.

Thyroglobulin DISORDERS OF THE THYROID

 Thyroglobulin is a protein synthesized and secreted Hypothyroidism
exclusively by thyroid follicular cells. This prohormone in  low free T4 level with a normal or high TSH— one of the
the circulation is proof of the presence of thyroid tissue, most common disorders of the thyroid gland, occurring in 5%
either benign or malignant. to 15% of women over the age of 65
 Thyroglobulin is currently measured by  When thyroid hormone is significantly decreased, symptoms
o double antibody RIA of cold intolerance, fatigue, dry skin, constipation,
o enzyme-linked immunoassay hoarseness, dyspnea on exertion, cognitive dysfunction, hair
o immunoradiometric assay loss, and weight gain have been reported.
o immunochemiluminescent assay method  On physical examination, those with severe hypothyroidism
may have low body temperature, slowed movements,
Thyroid Autoimmunity bradycardia, delay in the relaxation phase of deep tendon
 The most common cause of hyperthyroidism is an reflexes, yellow discoloration of the skin (from
autoimmune disorder called Graves’ disease. hypercarotenemia), hair loss, diastolic hypertension, pleural
 The antibody in this condition is directed at the TSH receptor and pericardial effusions, menstrual irregularities, and
and stimulates the receptor, leading to growth of the thyroid periorbital edema.
gland and production of excessive amounts of thyroid  Hypothyroidism may also lead to hyperlipidemia, most
hormone. notably when the TSH is greater than 10 mU/L.
 Tests for TSH receptor antibodies (TRAb, TSHRAb) can  Hypothyroidism can be divided into primary, secondary, or
detect antibodies directed against the TSH receptor whether tertiary disease, depending on the location of the defect.
they act to stimulate or block the TSH receptor.  The most common cause of hypothyroidism in developed
 Chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) countries is chronic lymphocytic thyroiditis, or Hashimoto’s
is at the other end of the thyroiditis.
autoimmune continuum.  Other common causes of hypothyroidism include iodine
deficiency, thyroid surgery, and radioactive iodine treatment
OTHER TOOLS FOR THYROID EVALUATION
Nuclear Medicine Evaluation
 Radioactive iodine - useful in assessing the metabolic TYPES OF HYPOTHYROIDISM
activity of thyroid tissue and assisting in the evaluation and Primary
treatment of thyroid cancer Thyroid gland dysfunction
 Radioactive iodine uptake (RAIU) - when radioactive Secondary
iodine is given orally, a percentage of the dose is taken up by Pituitary dysfunction
the thyroid gland. Tertiary
Hypothalamic dysfunction

CAUSES OF HYPOTHYROIDISM
Condition Comments
 If the RAIU is low in the presences of an undetectable TSH, Primary Chronic TPOAb or TgAb positive in
the differential diagnosis includes excess exogenous thyroid lymphocytic 80–99% of cases
hormone ingestion, high iodine intake, or a condition in thyroiditis
which stored thyroid hormone is leaking from the thyroid (Hashimoto’s
gland (typically in a setting known as subacute thyroiditis). thyroiditis)
 Radioactive iodine - useful in the evaluation of thyroid
nodules in the presence of a low or undetectable TSH
 suppression of ovulation in lactating postpartum Treatment for toxic History and physical
mothers goiter—subtotal examination (neck scar) are
thyroidectomy or key to diagnosis
Thyroid Ultrasound radioactive iodine
 capable of detecting even thyroid nodules of such a small
size as to be of unclear or even no clinical significance;
depending upon age, in up to 50% of clinically normal Excessive iodine
thyroid glands intake
 small <1cm) thyroid nodules can be seen History and urinary iodine
measurement useful

TRANSCRIBED BY: JOLAN HERCE

CLINICAL CHEMISTRY Jolan F. Herce
BSMT-3B
LECTURE / 2nd SEMESTER
Subacute thyroiditis
 Fatigue, weakness, decreased exercise tolerance
Usually transient
 Weight loss
Secondary Hypopituitarism Caused by adenoma,
 Heat intolerance
radiation therapy, or
destruction of pituitary  Hyperdefecation
 Menstrual changes (oligomenorrhea)
Tertiary Hypothalamic Rare  Prominence of eyes
dysfunction
Graves’ Disease
 Graves’ disease is the most common cause of thyrotoxicosis.
American Thyroid Association Guidelines for Hypothyroidism It is an autoimmune disease in which antibodies are produced
Screening Measurement of TSH that activate the TSH receptor.
o At age 35  Features of Graves’ disease include:
o Every 5 years after the age of 35 o Thyrotoxicosis
o More frequently with risk factors or symptoms: o Goiter
goiter, family history, lithium use, amiodarone use o ophthalmopathy (eye changes associated with
 Hypothyroidism is treated with thyroid hormone replacement inflammation and infiltration of periorbital tissue)
therapy. o dermopathy (skin changes in the lower extremities
 Levothyroxine (T4) is the treatment of choice. that have an orange peel texture)
 In primary hypothyroidism, the goal of therapy is to  Women are five times more likely than men to develop this
achieve a normal TSH level. condition.
 If hypothyroidism is secondary or tertiary in origin, TSH  Findings in Graves’ ophthalmopathy can include:
levels will not be useful in managing the condition and a mid- o orbital soft tissue swelling
o injection of the conjunctivae
o proptosis (forward protrusion of the eye, secondary to
infiltration of retroorbital muscles and fat)
o double vision (secondary to orbital muscle
involvement and fibrosis)
o corneal disease (often related to difficulty closing the
eyelids)

 Treatment of Graves’ ophthalmopathy: surgical

decompression of the orbits to prevent optic nerve injury and
blindness.
normal free T 4 level becomes the target of therapy.
 Levothyroxine has a half-life of approximately 7 days. Toxic Adenoma and Multinodular Goiter
 Toxic adenomas and multinodular goiter
o two relatively common causes of hyperthyroidism
o caused by autonomously functioning thyroid tissue.
Thyrotoxicosis  Treatment:
 Thyrotoxicosis is a constellation of findings that result when o Surgery
peripheral tissues are presented with, and respond to, an o radioactive iodine
excess of thyroid hormone. o medication (PTU or MMI)
 Thyrotoxicosis can be the result of excessive thyroid Although the medications can block thyroid hormone production,
hormone ingestion, leakage of stored thyroid hormone from they are not expected to lead to remission in these two conditions.
storage in the thyroid follicles.  When radioactive iodine is given, it tends to destroy only the
 The latter form of thyrotoxicosis is called hyperthyroidism. hyperactive (autonomous) portions of the thyroid gland, leaving
normal (sup- pressed) thyroid tissue undamaged.
SIGNS
 Tachycardia DRUG-INDUCED THYROID DYSFUNCTION
 Tremor Amiodarone-Induced Thyroid Disease
 Warm, moist, flushed, smooth skin  Amiodarone
 Lid lag, widened palpebral fissures o used to treat cardiac arrhythmias
 Ophthalmopathy (Graves’ disease) o fat-soluble drug with a long half-life (50 days) in the body
 Goiter that interferes with normal thyroid function
 Brisk deep tendon reflexes  Iodine, when given in large doses, leads to acute inhibition of
 Muscle wasting and weakness thyroid hormone production.
 Dermopathy/pretibial myxedema (Graves’ disease)  This is called the Wolff-Chaikoff effect. Amiodarone also blocks
 Osteopenia, osteoporosis T4-to-T3 conversion. The combination of these two actions leads
Symptoms to hypothyroidism in 8% to 20% of patients on chronic
 Nervousness, irritability, anxiety amiodarone therapy.
 Tremor
 Palpitations Subacute Thyroiditis

TRANSCRIBED BY: JOLAN HERCE

CLINICAL CHEMISTRY Jolan F. Herce
BSMT-3B
LECTURE / 2nd SEMESTER
 These conditions are often associated with a thyrotoxic
phase when thyroid hormone is leaking into the circulation, a
hypothyroid phase when the thyroid gland is repairing itself.
 Postpartum thyroiditis - most common form of subacute
thyroiditis. It occurs in 3% to 16% of women in the
postpartum period.
 Painful thyroiditis, also called subacute granulomatous
thyroiditis, subacute nonsuppurative thyroiditis, or de
Quervain’s thyroiditis, is characterized by neck pain, low-
grade fever, myalgia, a tender diffuse goiter, and swings in
thyroid function tests (as discussed earlier).

NONTHYROIDAL ILLNESS
 Hospitalized patients, especially critically ill patients, often
have abnormalities in their thyroid function tests.
 Typically, the laboratory pattern is one of low total T4, free
T4, and (sometimes) TSH.
 llness decreases 5′-monodeiodinase activity, less T4 is
converted to active T3. This leads to decreased levels of T3
and higher levels of rT3. There also seems to be an element
of central hypothyroidism and thyroid hormone– binding
changes associated with severe illness.

THYROID NODULES
 Thyroid nodules are common. Clinically apparent thyroid
nodules are present in 6.4% of adult women and 1.5% of
adult men, according to the Framingham data.
 Thyroid ultrasound finds unsuspected thyroid nodules in
20% to 45% of women and 17% to 25% of men.
 The major concern with thyroid nodules is that they may
represent a thyroid cancer. Fortunately, only 5% to 9% of
thyroid nodules prove to be thyroid cancer. FNA of these
nodules, with cytologic examination of the aspirate, has
become a routine practice to help distinguish the nodules that
require surgical removal from those that do not.

TRANSCRIBED BY: JOLAN HERCE